Overview: Trypanosoma cruzi is an intracellular
protozoan that causes Chagas' disease or trypanosomiasis, a very
serious problem in South and Central America (Figure
1).
T. cruzi is transmitted to humans and
various mammalian hosts by hematophagous
reduviid bugs when T. cruzi
trypomastigotes present in the insect's feces
enter the human host through breaks in the skin
(the insect bite) or mucous membranes and
subsequently infect macrophages and other human
cells. Chagas’ disease is potentially fatal in
humans and widely prevalent in animals, both
wild and domestic. Currently 16 to 18 million
people are infected with the
disease.

Figure 1. Trypanosoma cruzi trypomastigote in
blood smear.

Morphology: T. cruzi is a single-celled organism
that exists in three distinct forms, namely, the
infectious trypomastigote found in the
bloodstream, the intracellular amastigote
found in tissues, and the reproductive
epimastigote found in the reduviid insect.
Each form has the same basic morphological
characteristics, with slight variations in
physiology. Each cell contains a nucleus
containing its genetic material, and a single
tubular mitochondrion, which houses its own DNA, cristae, and enzymes, located within the
kinetoplast. The kinetoplast is a distinguishing
features of this group of species and is
composed of a fibrous network of DNA comprising
25% of the parasite's total DNA. In the
trypomastigote stage, the kinetoplast is
basket-shaped due to an odd arrangement of DNA
loops, while in amastigotes it is rod-shaped.
Infectious trypomastigotesfound in
blood grow to approximately 20 mm (millimetres)
long and are very slender with a thin, irregular
shaped outer membrane and central nucleus. The
flagellum stems from the kinetoplast, which is
located toward the posterior of the cell, and
runs through the remainder of the organism to
the flagellar pocket compartment before emerging
from the cell. When viewed under light
microscopy, trypomastigotes are usually seen in
a ‘C’ or ‘U’ shape. The reproductive
epimastigote stage is similar to the
trypomastigote, but the kinetoplast is located
anterior to the nucleus. In the intracellular
amastigote stage, however, the cells are round
instead of elongated, and the flagellum is
almost
unapparent.

Life Cycle and
Pathogenicity: The life cycle of T.
cruzi begins in an animal reservoir,
usually mammalian, either wild or domestic, and
includes humans. The vector of transmission is
the reduviid bug, or assassin bug (Figure
2). While feeding
on a host, the T. cruzi-infected bug
defecates, discharging infective trypomastigotes
in the feces. The trypomastigotes enter the bite
wound, mucous membranes, or conjunctivae and
infect a wide variety of cells. An indurated
inflammatory lesion (chagoma) often appears at
the site of the bit and parasite entry. Within
host cells the trypomastigotes transform into
amastigotes, replicating until the host cells
rupture to release additional parasites.
Trypomastigotes in the circulation can be
ingested by reduviid bugs during a blood meal,
thereby continuing the parasite life cycle.
The life cycle of T. cruzi is
summarized in
Figure 3.

Figure 2. Triatoma infestans or the “Kissing
Bug”, “Assassin Bug”, or “Cone-Nose Bug”, is a
vector for Chagas' disease.

Figure 3.
This illustration depicts the life cycle of
Trypanosoma cruzi. Click to enlarge.

Clinical Infection:
Chagas' disease can also be transmitted by blood
transfusion because of the stages in the
bloodstream. Early in the disease, heavy
infection of the cardiac muscle occasionally
cause acute heart failure and sudden cardiac
death (Figure 4). The pathogenesis of chronic Chagas'
disease is not well understood, but myocardial
inflammation, fibrosis, and atrophy can develop
with few or no detectable parasites. In some
patients, focal inflammation and destruction of
the myenteric nerve plexus of the gut result in
loss of peristalsis and enormous dilation of the
esophagus or colon. Since T. cruzi
antigens are processed via the endogenous
antigen-presentation pathway involving MHC class
I molecules (like viruses), a strong cytotoxic
CD8+ response to infection is
required to absolve an infected host from
disease.

Figure 4. Trypanosoma cruzi
in monkey heart.

The acute phase of T. cruzi infection
may result in a mild fever and swelling at the
entry site, but often infection and the
subsequent latency period are asymptomatic.
Chronic infection can go unnoticed for decades
and approximately 30% of those infected will
suffer life threatening complications. T.
cruzi goes to great lengths to avoid its
host’s immune response, producing a protein
called parasite-derived neurotrophic factor
(PDNF) that activates anti-apoptotic molecules
within infected cells. Chronic symptoms include
megacolon, megaesophagus, conduction
abnormalities (damaged nerves in the heart),
epicardial lesions (reaction to chronic
inflammation of the heart), cardiac
manifestations (fibrosis of damaged cardiac
tissue), and sudden death by heart failure.

Treatment: There are two
approaches to treating Chagas' disease, namely,
antiparasitic treatment, to kill the parasite
and symptomatic treatment, to manage the
symptoms and signs of infection. Antiparasitic
treatment is most effective early in the course
of infection, but is not limited to cases in the
acute phase. Drugs of choice include azole or
nitro derivatives such as benznidazole or
nifurtimox. Both agents are limited in their
capacity to effect parasitologic cure (a
complete elimination of T. cruzi from
the body), especially in chronically infected
patients, and resistance to these drugs has been
reported. Studies suggest that antiparasitic
treatment leads to parasitological cure in about
60-85% of adults and more than 90% of infants
treated in the first year of acute phase Chagas
disease. Children (age 6 to 12 years) with
chronic disease have a cure rate of about 60%
with benznidazole. While the rate of cure
declines the longer an adult has been infected
with Chagas' disease, treatment with
benznidazole has been shown to slow the onset of
heart disease in adults with chronic Chagas
infections.